Microwave-Assisted P-C Coupling of the Less Reactive Chlorobenzene and >P(O)H Reagents in the Absence of the Usual...

The so far unattended version of the Hirao reaction involving the coupling of the less reactive chloroarenes with >P(O)H reagents, such as diarylphosphine oxides, diethyl phosphite, and ethyl phenyl-H-phosphinate, was investigated in detail using Pd(OAc)₂ as the catalyst precursor, and applying some excess of the P-reagent to provide the ligand via its trivalent tautomeric (>P-OH) form. In the presence of triethylamine, no P-C coupling took place, meaning that there was a need for a stronger base, an alkali carbonate. The solvent had a significant effect on the efficiency of the Hirao reaction. The optimum conditions (10% of the Pd(OAc)₂, 1.3 equiv. of the P-reagent, 1.1 equiv. of the alkali carbonate, 135-150 °C) explored herein were applied in the synthesis of diaryl-phenylphosphine oxides, aryl-diphenylphosphine oxides, diethyl arylphosphonates, and ethyl diphenylphosphinate. Theoretical calculations performed at the M06-2X/6-31G(d,p)[PCM(MeCN)] level also justified coupling with the chloroarenes under appropriate conditions, and were in accord with the experimental results revealing the unsuitability of triethylamine as a base and the need for an alkali carbonate. The new protocol elaborated herein is more practical and "greener" than the version with bromoarenes, and embraces a wide substrate scope.